EA EARL RLY Y LUN UNG G CANC ANCER ER Pang Yong Kek Lecture - - PowerPoint PPT Presentation

SCREENING FOR EA EARL RLY Y LUN UNG G CANC ANCER ER

Pang Yong Kek

Lecture Outline

■ Why performing screening? ■ How to improve early detection? ■ Benefits and Risks of screening ■ Challenges in screening ■ Conclusion

Why Performing Screening?

■ Lung cancer is one of the commonest cancer afflicting mankind ■ Vast majority of the victims have advanced disease at the time of presentation ■ Despite the significant improvement made in treatment modality, mortality of lung cancer remains high – In 2018, it is estimated that 154,050 deaths from lung cancer will occur in the United States. – Five-year survival rates for lung cancer are only 18%

Lung cancer

In Malaysia, lung cancer accounts for

• 13.8% of all cancers in

males and

• 3.8% of all cancers in

females

Second Report of the National Cancer Registry. Cancer incidence in Malaysia, 2003. National Cancer Registry, Malaysia (http:www.acrm.org.my/ncr)

Clinical stage of NSCLC at diagnosis - UMMC

No of patients

76% of patients with NSCLC present with stage III or stage IV disease

Stage of disease

n = 580

• 1. Liam CK et al. Respirology 2000; 5:355-61; 2. Liam CK et al. Chest 2002; 121:309-10

Stage 3b & 4 = 69% Stage 3a, 7%

(37%) (32%)

Why Performing Screening?

■ Screening often leads to detection of early stage disease ■ Early stage disease = Higher chance curative treatment = Better Life Expectancy + Improved Quality of Life

How To Screen?

■ Most of the early lung cancer does not have any sign or symptom, ■ Imagi ging g of the chest t has been regarded as a potentially useful tool to identify the nodule in the lung ■ Historical study: CXR R & sputum utum cytology logy versus standard of care has failed to demonstrate survival benefit in high risk individuals

1. Moyer VA, Force USPST. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014;160:330–338. 2. Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e78S–92S.

How To Screen?

■ In recent years, due to advances made in imaging technology, the idea has been re-investigated using low-dose CT scan (LDCT)

Source: The Valley Health Cancer Center website

NLST Study

■ The National Lung Screening Trial (NLST) is a trial conducted on over 53,000 high-risk individuals in the US. ■ They are defined as – Aged 55–74 years – Current smokers or – Ex-smokers (who had quit ≤ 15 years) – 30 pack-years

NLST Study

■ Subjects were randomised for screening with LDCT Thorax versus Chest X-ray ■ Each subject will get ≥ 3 scans (baseline and annually for 2 years) ■ After that they were followed up for another 3.5 years Result: ■ the LDCT arm showed a 20% (95% CI, 6.8–26.7; P=.004) reduction in mortality from lung cancer compared to the CXR

Tobacco and Risk of Lung Cancer

■ The overall relative risk (RR) for lung cancer is ≈ 20-fold higher for smokers than for non-smokers. ■ In general, the more tobacco is smoked, the higher is the risk ■ Cessation of tobacco smoking decreases the risk for lung cancer.

Other Risk Factors of Lung Cancer

■ Although smoking tobacco is a well-established risk factor for lung cancer, other environmental and genetic factors also increase the risk These include: ■ Occupational exposure ■ History of lung or other cancers ■ Family history of cancer

Other Risk Factors - Occupational exposure

Carcinogens targeting the lungs include ■ arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, diesel fumes, coal smoke, and soot. Radon exposure

Other Risk Factors – Previous cancer

■ Patients with other cancers are also at increased risk of cancer, e.g. : – Survivors of primary lung cancer, lymphomas, cancers of the head and neck, or smoking-related cancers, such as bladder cancer. ■ Patients previously treated with chest irradiation have a 13 13-fold ld increased risk of developing a new primary lung cancer, ■ Those who have previously been treated with alkylating agents (chemotherapy) have an estimated RR of 9.4

Other Risk Factors - Family history of cancer

■ Several studies have shown the 1st degree relatives of a lung cancer patient are at increased risk of lung cancer ■ A meta-analysis of 28 case-control studies and 17 observational cohort studies showed an RR of 1. 1.8 (95% CI, 1.6–2.0) for individuals with a sibling/parents or a first-degree relative with lung cancer ■ The risk is greater in individuals with multi ltiple ple affected ed family ily members mbers or who had a cancer diagnosis at a young g age.

Selection of individuals for Screening

■ The NCCN Panel recommends that only those with high risk sk should be screened ■ Those with moderate or low risk should not be screened ■ In addition, only those who are the poten enti tial al candid idat ates es for curati ative therap rapy should be screened.

High Risk Patients

■ Group 1: – Individuals aged 55 to 74 years with a ≥ 30 pack-year history of smoking tobacco who currently smoke or, if former smoker, have quit within 15 years (category 1). ■ Group 2 – Individuals aged 50 y years or older der with a ≥ 20 pack-year history of smoking tobacco and with th one e addi ditional tional risk k factor

• r (category

2A). (Screening beyond the NLST criteria)

High Risk Patients

For Group 2, screening may be offered if they have one of the additional risk factors below: ■ personal history of cancer or lung disease, ■ family history of lung cancer, ■ radon exposure, ■ occupational exposure to carcinogens.

Benefits

■ Detection of early disease when it is still curable

– Although patients with earliest-stage disease (IA) may have a 5-year survival rate of ≈ 75% with surgery, the outcomes quickly decrease with increasing stages – In the NLST, 356 participants died of lung cancer in the LDCT arm and 443 participants died of lung cancer in the chest radiograph arm. – To prevent 1 death from lung cancer, 320 individuals with high-risk factors must be screened with LDCT.

Benefits

■ Improved survival

Benefits

■ Improved quality of life – as a result of

– Early disease detection and curative treatment

■ The NLST found that 40% of the cancers detected in the CT-screening group were stage IA, 12% were stage IIIB, and 22% were stage IV. ■ Conversely, 21% of the cancers detected in the CXR group were stage IA, 13% were stage IIIB, and 36% were stage IV.

■ These results suggest that LDCT screening decreases the number of cases of advanced

National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409.

Benefits

■ Identification of other treatable disease, e.g. COPD, coronary artery disease

National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409.

Benefits

■ Long-term cost may be reduced – Upfront costs, e.g. screening, additional diagnostic procedures and other interventions will increase; however – Future costs of treating advanced diseases with chemotherapy, targetable agents, immunotherapy, radiation therapy and others will be reduced

Benefits

■ Provide an opportunity to persuade chronic smokers to stop smoking

Risks/Harms

■ Screening leads to identification of many false positive nodules, which result in many unnecessary interventions – In the NLST, the false-positive rate was 96.4% for the CT screening group. – This is reduced to 33% with 2 annual sequential LDCT. – Those who were screened positive may require interval imaging, percutaneous needle biopsy, or even surgical biopsy

Risks/Harms

■ Some of these procedures are not without any risk – the average surgical mortality rate for major lung surgery across the US is 5% 5%, and the frequency of serious complications is > > 20%.

Risks/Harms

■ False-negative results – may delay or prevent diagnosis and treatment because of a false sense of good health

Risks/Harms

■ Futile detection of small aggressive tumour ■ Futile detection of indolent disease (over-diagnosis)

Risks/Harms

■ Identification of any nodule will lead to anxie iety ty for the screened subjects ■ False se-posi positiv tive and indeterm erminat inate results sults may decrease quality of life because of mental tal anguish uish and additio tional nal testin sting

Risks/Harms

■ Risk sk of radiat iation ion ■ Using low-dose techniques, the mean effective radiation dose is 1.5 mSv (SD ± 0.5 mSv) compared with an average of 7 mSv for conventional CT scan ■ The radiation dose of LDCT is 10 X X that of CXR ■ Brenner et al estimated a 1.8% increase in lung cancer cases if 50%

• f all current and former smokers in the US between 50 and 75 years
• f age were to undergo annual screening LDCT.

Cost-effectiveness

■ The cost-effectiveness of LCS is also important to consider. LDCT imaging is more re expen ensiv sive e than many other screening programs, and therefore it is important to validate the effectiveness of screening. ■ 7 analyses have reported a cost effectiveness ratio of $100,000 (in U.S. dollars) or less per quality adjusted life years gained for LDCT. ■ A threshold level of $100,000 per quality-adjusted life year gained is what some experts consider to be a reasonable value in the United States

Other Challenges

■ Screening of early cancer is not a substitute for effort to promote smoking cessation ■ In fact, it should be used an opportunity to pursuit subject to quit smoking (if they are still smoking)

Other Challenges

■ Early lung cancer screening has not been prospectively tested in this country ■ Lack of resources (time for counselling, CT machine and interventionists) ■ Many high risk individuals are non-smoker, and younger than those traditionally included in the trial (< 50 - 55 years old) ■ TB is common in this part of the world and this may result in a lot of false positive cases

Future opportunity

■ Can we increase to sensitivity and specificity of the screening test? – Combination with sputum test or breath test – Combination with blood test

Future opportunity

■ Can we increase to sensitivity and specificity of the screening test? – PET-CT CT scan?

■ PET-CT has been shown to increase the specificity for malignancy (7 – 10mm) ■ PET has low sensitivity for nodules with < 8 mm of solid component and for small nodules near the diaphragm.

Conclusion

■ Recent NLST has shown positive result for early lung cancer screening by employing LDCT. ■ However, 3 other trials: MILD LD (Multicentre Italian Lung Detection), DAN ANTE TE (Detection And screening of early lung cancer with Novel imaging TEchnology), Danish sh Lun ung Cancer cer Screen eening ing Trial (all using the LDCT) did not show a positive outcome in term

• f mortality

■ Before such screening is being performed here, every aspect of the programme should be explored and deliberated.